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INTRODUCTION: Secernin‐1 (SCRN1) is a neuronal protein that co‐localizes with neurofibrillary tangles in Alzheimer's disease (AD), but not with tau inclusions in corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), or Pick's disease. METHODS: We measured SCRN1 concentration in cerebrospinal fluid (CSF) using a novel mass spectrometric parallel reaction monitoring method in three clinical cohorts comprising patients with neurochemically characterized AD (n = 25) and controls (n = 28), clinically diagnosed Parkinson's disease (PD; n = 38), multiple system atrophy (MSA; n = 31), PSP (n = 20), CBD (n = 8), healthy controls (n = 37), and neuropathology‐confirmed AD (n = 47). RESULTS: CSF SCRN1 was significantly increased in AD (P < 0.01, fold change = 1.4) compared to controls (receiver operating characteristic area under the curve = 0.78) but not in CBD, PSP, PD, or MSA. CSF SCRN1 positively correlated with CSF total tau (R = 0.78, P = 1.1 × 10−13), phosphorylated tau181 (R = 0.64, P = 3.2 × 10−8), and Braak stage and negatively correlated with Mini‐Mental State Examination score. DISCUSSION: CSF SCRN1 is a candidate biomarker of AD, reflecting tau pathology. HIGHLIGHTS: We developed a parallel reaction monitoring assay to measure secernin‐1 (SCRN1) in cerebrospinal fluid (CSF).CSF SCRN1 was increased in Alzheimer's disease compared to healthy controls.CSF SCRN1 remained unchanged in Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, or corticobasal degeneration compared to controls.CSF SCRN1 correlated strongly with CSF phosphorylated tau and total tau.CSF SCRN1 increased across Braak stages and negatively correlated with Mini‐Mental State Examination score. [ABSTRACT FROM AUTHOR]

Urbanization can influence local richness (alpha diversity) and community composition (beta diversity) in numerous ways. For instance, reduced connectivity and land cover change may lead to the loss of native specialist taxa, decreasing alpha diversity. Alternatively, if urbanization facilitates nonnative species introductions and generalist taxa, alpha diversity may remain unchanged or increase, while beta diversity could decline due to the homogenization of community structure. Wetlands and ponds provide critical ecosystem services and support diverse communities, making them important systems in which to understand the consequences of urbanization. To determine how urban development shapes pond community structure, we surveyed 68 ponds around Madison, Wisconsin, USA, which were classified as urban, greenspace, or rural based on surrounding land use. We evaluated how landscape and local pond factors were correlated with the alpha diversity of aquatic plants, macroinvertebrates, and aquatic vertebrates. We also analyzed whether surrounding land use was associated with changes in community composition and the presence of specific taxa. We found a 23% decrease in mean richness (alpha diversity) from rural to urban pond sites and a 15% decrease from rural to greenspace pond sites. Among landscape factors, adjacent developed land, mowed lawn cover, and greater distances to other waterbodies were negatively correlated with observed pond richness. Among pond level factors, habitat complexity was associated with increased richness, while nonnative fishes were associated with decreased richness. Beta diversity was relatively high for all ponds due to turnover in composition between sites. Urban ponds supported more nonnative species, lacked a subset of native species found in rural ponds, and had slightly higher beta diversity than greenspace and rural ponds. Our results suggest that integrating ponds into connected greenspaces, maintaining riparian vegetation, preventing nonnative fish introductions, and promoting habitat complexity may mitigate the negative effects of urbanization on aquatic richness. While ponds are small in size and rarely incorporated into urban conservation planning, the high beta diversity of distinct pond communities emphasizes their importance for supporting urban biodiversity. [ABSTRACT FROM AUTHOR]

Background: At present, there are limited fluid biomarkers which measure the underlying pathophysiology of frontotemporal dementia (FTD). Approximately a third of people with FTD have a genetic cause where the pathological basis is well understood. Studying fluid biomarkers in these genetic forms therefore allows greater insight into the relationship between the measure and the underlying disease mechanism. Based on prior work identifying synaptic and lysosomal dysfunction as common mechanisms across the different forms of FTD, we performed a targeted search of proteins related with synapses and the lysosomal pathway on an unbiased proteomic dataset generated from the GENetic FTD Initiative (GENFI) study. Method: The dataset was obtained from a total of 248 cerebrospinal fluid samples (CSF) from the GENFI cohort including 109 presymptomatic (44 C9orf72, 39 GRN, 26 MAPT) and 63 symptomatic (34 C9orf72, 17 GRN, 12 MAPT) mutation carriers as well as 76 mutation‐negative controls where Tandem Mass Tag (TMT) proteomics had been performed. We selected the clusters obtained from a Gene Ontology analysis that corresponded to the terms "synapse" and "lysosome" and generated a list of proteins related to each category. We then analysed the differences in each specific protein between genetic groups. Result: A total of 42 of the synaptic proteins preselected were significantly changed in symptomatic MAPT mutation carriers, 70 in symptomatic GRN mutation carriers, and 92 in the symptomatic C9orf72 group. Among all of these, there were only 9 proteins that overlapped in the three genetic forms. This list included reelin, which was significantly decreased in each symptomatic group when compared to controls (MAPT p‐value = 0.0016, GRN = 0.0008, C9orf72 = 0.0064), and calretinin, which was significantly increased in symptomatic groups compared to controls (MAPT = 0.0260, GRN = 0.0000, C9orf72 = 0.0100). We then used the same approach to study lysosomal proteins, and found that 38 proteins were significantly changed in symptomatic MAPT, 31 in the symptomatic GRN group and 41 in symptomatic C9orf72 expansion carriers. Conclusion: This study provides new insights into candidate markers to assess synaptic and lysosomal dysfunction in FTD. [ABSTRACT FROM AUTHOR]

Background: Pathogenic mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), inducing a reduced biofluid concentration of the progranulin protein (PGRN). PGRN is a cysteine‐rich glycoprotein with essential roles in inflammation and lysosomal function, made up of 7 granulin peptides and 1 paragranulin. The role of these peptides is unclear, but existing data suggests they may have contradictory roles to full‐length PGRN. With the development of numerous clinical trials aiming to treat progranulin‐associated FTD (FTD‐GRN) by increasing full‐length PGRN, it is important to establish effective outcome measures to assess treatment success and further our understanding of PGRN's biology. Here, we aimed to develop an assay to quantify granulin peptides in cerebrospinal fluid (CSF) and determine whether they contribute to the pathology of FTD‐GRN. Method: Based on previously published explorative data of endogenous CSF peptides, 12 peptides spanning the progranulin sequence, were selected for the development of targeted assays using a quadrupole Orbitrap hybrid mass spectrometer (Fusion Tribrid, Thermo). An analytical protocol was optimised involving reduction, alkylation, molecular weight cut‐off filtration and solid phase extraction, and using isotope labelled heavy standards for quantification. Additionally, tandem mass tag (TMT) proteomics was used to analyse tryptic peptides spanning granulin and paragranulin sequence regions in 248 CSF samples from the Genetic FTD initiative (GENFI) including 56 GRN mutation carriers and 76 mutation‐negative controls. Result: Preliminary results reveal the presence of three endogenous peptides in CSF, which based on sequence matching, likely represent granulin 6 and 7 alongside the paragranulin peptide. TMT results showed significantly reduced relative peptide intensity across the granulin regions in GRN carriers CSF compared to controls (p<0.0001), but no significant difference in the paragranulin region (p>0.33). Conclusion: These findings indicate that two granulins and paragranulin are quantifiable in CSF and may have key roles in progranulin biology and potentially FTD pathology. This is supported by TMT results of differential CSF paragranulin levels compared to granulins. Continuing work will quantify CSF granulin concentrations in the GENFI cohort to assess whether these peptides have key roles in FTD‐GRN's underlying biology and as potential outcome measures in trials. [ABSTRACT FROM AUTHOR]

Vegetation productivity is increasing in the U.S. Northern Great Plains but decreasing in some nearby Northern Rocky Mountain grasslands due to increases in aridity. It is unclear if decreases to montane grassland productivity from drying autumns can be partly offset by late‐season green‐ups after precipitation events. These include the multiple snowfall and snowmelt periods that often characterize the summer‐to‐winter transition, but are difficult to observe due to logistical constraints. Here, we quantify changes to vegetation indices and ecosystem carbon uptake that occurs after snowfall and melt in climatological autumn in a montane grassland in Montana, USA using eddy covariance, phenological camera, and remote sensing analyses. Carbon dioxide flux follows a diurnal pattern after autumn snowmelt events despite overall ecosystem C loss, suggesting that post‐snowmelt photosynthesis helps dampen C loss during autumn and provides fresh photosynthate to support ecosystem functioning. Light‐saturated photosynthesis after three snow events was not statistically different than before snowfall (∼6 μmol CO2 m−2 s−1 in 2016 and ∼2.5 μmol CO2 m−2 s−1 in 2017). Observations are consistent with the notion that canopy photosynthesis is resistant, rather than resilient, to autumn snow. MODIS indicates that post‐snow greenups can occur, but not every year. Such events likely play a small role in the annual ecosystem carbon balance but may be disproportionately important for organisms faced with dwindling late‐season forage. Future efforts should seek to understand the community and ecosystem consequences of vegetation functioning during autumn as part of an expanded effort to understand phenological changes during this under‐studied and changing time of year. Plain Language Summary: The productivity of some montane meadows in the U.S. Northern Rockies has decreased over the past 50 years due to increases in aridity. This is of concern for the ecosystem services that these grasslands provide like forage to help animals overwinter. Our understanding of the full annual carbon cycle of many montane ecosystems is incomplete because research sites can be difficult to access when snow is intermittent, as is often the case during autumn in the Northern Rockies. This is one of the many reasons why autumn is underrepresented in climate change studies. We used automated measurement systems to measure ecosystem carbon dioxide flux and vegetation greenness during the autumn‐to‐winter transition in a montane meadow in Montana, USA. Ecosystem carbon uptake after two or more snowfall and melt periods was the same as before snowfall during two consecutive years. This suggests that montane grassland photosynthesis is resistant to short‐lived snow events. Our results demonstrate that autumn snow and melt events neither help nor substantially hinder mountain meadow grass photosynthesis, which helps us understand the ecosystem services they provide. Key Points: Mountain meadow carbon uptake persists after autumn snowfall and melt eventsAutumn snowfall appears to be a minor ecosystem disturbance against which grass photosynthesis is resistant [ABSTRACT FROM AUTHOR]

Lacustrine δ2H and δ18O isotope proxies are powerful tools for reconstructing past climate and precipitation changes in the Arctic. However, robust paleoclimate record interpretations depend on site‐specific lake water isotope systematics, which are poorly described in the eastern Canadian Arctic due to insufficient modern lake water isotope data. We use modern lake water isotopes (δ18O and δ2H) collected between 1994–1997 and 2017–2021 from a transect of sites spanning a Québec‐to‐Ellesmere Island gradient to evaluate the effects of inflow seasonality and evaporative enrichment on the δ2H and δ18O composition of lake water. Four lakes near Iqaluit, Nunavut sampled biweekly through three ice‐free seasons reflect mean annual precipitation isotopes with slight evaporative enrichment. In a 23° latitudinal transect of 181 lakes, through‐flowing lake water δ2H and δ18O fall along local meteoric water lines. Despite variability within each region, we observe a latitudinal pattern: southern lakes reflect mean annual precipitation isotopes, whereas northern lakes reflect summer‐biased precipitation isotopes. This pattern suggests that northern lakes are more fully flushed with summer precipitation, and we hypothesize that this occurs because the ratio of runoff to precipitation increases with latitude as vegetation cover decreases. Therefore, proxy records from through‐flowing lakes in this region should reflect precipitation isotopes with minimal influence of evaporation, but vegetation changes in lake catchments across a latitudinal transect and through geologic time may influence the seasonality of lake water isotopic compositions. Thus, we recommend that future lake water isotope proxy records are considered in context with temperature and ecological proxy records. Plain Language Summary: Proxies from sediment cores that reflect the isotopic composition of lake water are commonly used to reconstruct past climate, but understanding the processes affecting lake water isotopes (e.g., the seasonal distribution of precipitation and evaporation) is key to accurate climate interpretations. However, due to accessibility issues, little is known about the seasonal isotopic composition of water in eastern Canadian Arctic lakes. Here, we compile modern lake water isotope (δ18O and δ2H) measurements spanning the eastern Canadian Arctic, with special focus on Baffin Island, collected in 1994–1996 and 2017–2021, to identify regional and seasonal patterns in lake water isotopes. Isotopes from lakes in the southern part of this transect reflect mean annual precipitation with some influence of evaporation. In contrast, lakes in the northern part of this transect reflect summer precipitation isotopes. This latitudinal trend may be caused by vegetation cover: as vegetation becomes less dense northward, relatively more precipitation in a catchment enters the lake as runoff. Despite this trend, there is some variability within each region. Therefore, quantifying lake water isotope seasonality is a critical step toward robust interpretations of lake water isotope proxy records. Key Points: Eastern Canadian Arctic lakes reflect precipitation isotopes with little influence of evaporative enrichmentPatterns in lake water isotope seasonality driven by the ratio of runoff to precipitationGroundwater is an important variable in the lake system that influences lake water isotope seasonality [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate whether sedative medications are associated with adverse outcomes in people with dementia, and whether specific characteristics of these medications predict a higher risk of harm. Method: A retrospective cohort study was carried out of 15,210 patients diagnosed with dementia between 2008 and 2017 in South London. From recorded medications at dementia diagnosis, we ascertained those with drowsiness listed as a side effect (termed 'sedative' hereafter) and subdivided them by frequency and strength of sedation, receptor profile, half‐life and whether they were psychotropics. Multivariable Cox regression models were applied to determine risk of mortality and emergency hospitalisation, and generalised estimating equations to investigate cognitive decline. Final models were adjusted for 19 potential confounders, including measures of physical and mental health, functioning and central anticholinergic burden. Result: At diagnosis 70.4% of patients with dementia were receiving at least one sedative medication. Median survival time was 4.0 years and median time to first hospitalisation 1.4 years. After controlling for potential confounders, receipt of any sedative medication at dementia diagnosis was associated with accelerated cognitive decline and a higher hospitalisation risk, but only medications with a cautionary warning yielded an increased mortality hazard. Medications acting through gamma‐aminobutyric acid agonism, psychotropic sedatives and those with a short half‐life were associated with a higher risk of mortality. Gamma‐aminobutyric acid agonists, N‐methyl‐D‐aspartate receptor antagonists and non‐psychotropic sedatives were associated with an increased hospitalisation risk. Alpha‐1 antagonist, antihistamines, N‐methyl‐D‐aspartate receptor antagonists, psychotropic sedatives, and those with shortest or longest half‐life were associated with accelerated cognitive decline. Conclusion: Receipt of any sedative agent was associated with hospitalisation and accelerated cognitive decline. Differences in hazard appear to exist between frequency/strength of sedation, receptor profiles, half‐life, and prescribing indication. These differences should be taken into consideration in medication reviews at the time of dementia diagnosis. [ABSTRACT FROM AUTHOR]

Background: A hallmark of neurodegenerative disorders is synaptic dysfunction and degeneration. This makes the presynaptic protein synaptosomal‐associated protein 25 (SNAP‐25) and the Vesicle‐associated membrane protein 2 (VAMP‐2) targets of interest and importance. Previously, these proteins have only been measurable in cerebrospinal fluid (CSF) and are increased in Alzheimer's disease (AD) patients. Considering the advancement of blood‐based detection of phosphorylated tau (p‐tau), neurofilament light (NfL) and amyloid‐β (Aβ42/40), a measure of synaptic degeneration in blood would be important for disease prognosis and clinical trial outcome. In this study, we describe results from novel single molecular arrays (Simoa) for blood SNAP‐25 and VAMP‐2. Method: Prototype Simoa assays for N‐terminal SNAP‐25 and VAMP‐2 were developed as more sensitive versions of previously validated in‐house CSF assays with diluent suited for both plasma and CSF. We examined 110 participants (54 AD and 56 healthy controls) from the Swedish BioFINDER pilot study. The mean age of patients was 75.9 years (7.1 SD) and there was an even distribution of sex. We examined group differences by the Wilcoxon rank sum test and associations between these two blood biomarkers and Aβ‐PET, tau‐PET, MRI and MMSE were determined by linear regression, adjusting for age and sex. Result: SNAP‐25 was significantly increased in patients with AD (mean [SD], 0.81 pg/mL [0.27]; p < 0.001) as compared to controls (0.60 pg/mL [0.22]). SNAP‐25 distinguished AD patients from controls with an area under the curve of 0.74 (95% CI = 0.65‐0.83). SNAP‐25 showed association with Aβ PET (β = 0.10, p = 0.007) but not tau PET. SNAP‐25 associated with cortical thickness (β = ‐0.05, p = 0.009) and MMSE (β = ‐6.69, p = 0.001). No significant associations were found when analysing the AD group alone. VAMP‐2 showed no significant association with any of the mentioned parameters above. Conclusion: This novel ultra‐sensitive immunoassay demonstrates an increase of plasma SNAP‐25 in AD patients, and a significant relationship with cognition and cortical atrophy. Further studies will verify these changes in independent cohorts and explore the relationship between plasma SNAP‐25 and VAMP‐2 with synaptic vesicle glycoprotein 2A (SV2A) PET in a broad range of neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Background: Synaptic dysfunction and degeneration are believed to be among the earliest and most reliable indicators of cognitive impairment in neurodegenerative disorders, including Alzheimer's disease (AD). Discovering and verifying novel biomarkers that can quantify synaptic degeneration and serve as prognostic indicators would be valuable to track cognitive decline in clinical and drug trial settings. By using mass spectrometry, we have studied a panel of 17 synaptic proteins as potential biomarkers for AD and a broad range of neurodegenerative disorders. Of these proteins, neuronal pentraxin‐2 (NPTX2) has shown great promise as a synaptic biomarker, showing a decrease in symptomatic disease. Therefore, we aimed to develop a Single molecule array (Simoa) for NXPT2, a method more suited for routine clinical assessment than mass spectrometry‐based workflows. Method: We developed an in‐house NPTX2 Simoa assay on the HD‐X platform (Quanterix) with paramagnetic beads coupled with a rabbit monoclonal capture antibody (EPR24020‐38, Abcam) and biotinylated rabbit monoclonal detector antibody (EPR15618, Abcam), both specifically targeting NPTX2. Full‐length recombinant NPTX2 (7816‐NP‐050, Biotechne) was used as the calibrator. Using the assay, we analyzed 55 healthy controls (78.0 (6.5 SD) years) and 54 AD patients (73.5 (7.0 SD) years) using 2 uL cerebrospinal fluid (CSF) in the BioFINDER pilot study. Group comparisons were performed using the Wilcoxon rank sum test and linear models adjusted for age and sex were used to assess associations of NPTX2 protein levels with cognitive function (mini mental status exam (MMSE)) and with neuroimaging, e.g., Aβ‐PET, tau‐PET (temporal ROI, Braak I‐IV) as well as cortical thickness in an AD signature composed of temporal regions in the AD group. Result: CSF NPTX2 concentration was found to be lower in AD compared with controls (p = 0.017, Figure). Lower NPTX2 concentration was associated with greater tau PET SUVR (β(SD) = ‐0.25(0.079), p‐value = 0.0027) and cortical thickness atrophy (β(SD) = 0.075(0.024), p‐value = 0.0034)) but not with amyloid‐β PET SUVR. Lower NPTX2 concentration was also associated with lower MMSE score (β(SD) = 2.62 (0.75), p‐value = 0.0010). Conclusion: We have successfully developed a Simoa assay of a novel CSF biomarker, NPTX2. This semi‐automated method allows for large‐scale evaluation of NPTX2, a leading candidate for synaptic degeneration in neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD), defined by amyloid‐β (Aβ) and neurofibrillary tau tangles, can be viewed as a continuum, starting with an asymptomatic "pre‐clinical" phase that progresses to a symptomatic clinical stage characterized as mild cognitive impairment (MCI), and finally, AD dementia. Identifying biomarkers reflective of the different disease stages is important to detect individuals at risk of developing AD, to monitor disease progression and the effect of treatments, as well as to determine new therapeutic targets. Method: We present data from a cross‐sectional tandem mass tag (TMT) proteomic study of cerebrospinal fluid (CSF) samples from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort (young adults (n = 22), cognitively unimpaired (n = 54), cognitively impaired (n = 26), MCI (n = 19), AD (n = 19), non‐AD (n = 16), frontotemporal dementia (n = 9); total n = 214); a highly profiled cohort across the AD continuum with clinical and neuropsychological assessments, MRI, and Aβ and tau positron emission tomography (PET). To enhance detection of brain‐derived proteins, we evaluated the use of a TMT booster channel consisting of brain protein extract. Planned statistical analyses include linear regression modelling to compare biomarker distributions across groups, covariating for sex and age where appropriate as well as correlation analyses of biomarker levels with Aβ and tau PET measurements. Result: Our preliminary data analysis suggests that a set of proteins differed with high significance between amyloid PET negative and positive individuals (Fig. 1), including proteins that showed changes already at the pre‐clinical stage of AD. We will explore the correlation of the identified biomarker candidates with pathological process and disease progression, as well as with Aβ‐ and tau‐PET measurements. Also, protein changes associated with aging and other neurodegenerative disorders will be evaluated. Finally, the use of a TMT booster based on brain protein extract to enhance identification of CSF biomarkers will be assessed. Conclusion: This study describes the most extensive unbiased proteomic profiling in CSF across the AD continuum, identifying proteins that may serve as novel therapeutic targets and fluid biomarkers for the disease. Additionally, the use of a TMT booster to enhance the detection of brain‐derived proteins was evaluated. [ABSTRACT FROM AUTHOR]

The North American Breeding Bird Survey (BBS) provides data that can be used in complex, multiscale analyses of population change, while controlling for scale‐specific nuisance factors. Many alternative models can be fit to the data, but most model selection procedures are not appropriate for hierarchical models. Leave‐one‐out cross‐validation (LOOCV), in which relative model fit is assessed by omitting an observation and assessing the prediction of a model fit using the remainder of the data, provides a reasonable approach for assessing models, but is time consuming and not feasible to apply for all observations in large data sets. We report the first large‐scale formal model selection for BBS data, applying LOOCV to stratified random samples of observations from BBS data. Our results are for 548 species of North American birds, comparing the fit of four alternative models that differ in year effect structures and in descriptions of extra‐Poisson overdispersion. We use a hierarchical model among species to evaluate posterior probabilities that models are best for individual species. Models in which differences in year effects are conditionally independent (D models) were generally favored over models in which year effects are modeled by a slope parameter and a random year effect (S models), and models in which extra‐Poisson overdispersion effects are independent and t‐distributed (H models) tended to be favored over models where overdispersion was independent and normally distributed. Our conclusions lead us to recommend a change from the conventional S model to D and H models for the vast majority of species (544/548). Comparison of estimated population trends based on the favored model relative to the S model currently used for BBS summaries indicates no consistent differences in estimated trends. Of the 18 species that showed large differences in estimated trends between models, estimated trends from the default S model were more extreme, reflecting the influence of the slope parameter in that model for species that are undergoing large population changes. WAIC, a computationally simpler alternative to LOOCV, does not appear to be a reliable alternative to LOOCV. [ABSTRACT FROM AUTHOR]

Background: Mass spectrometry is used as reference method for protein quantification by measuring tryptic peptides derived from the target protein relative to a stable isotope‐labeled standard. Existing targeted mass spectrometric methods to measure total tau (tTau) and phosphorylated tau (pTau) species in cerebrospinal fluid (CSF) rely either on immunoaffinity enrichment of the protein or exploit the unusual property of tau being soluble in 2.5% perchloric acid (PA), to precipitate abundant sample proteins. Both strategies, however, carry risk of introducing bias: immunoaffinity enrichment relies on the specificity of the used antibodies, which may not have equal affinity for all of the large number of processed or modified forms of tau, and PA may partially precipitate some tau forms. To address this problem, we have developed an antibody‐ and PA‐free method to measure tau and pTau epitopes in CSF by targeted mass spectrometry. Method: CSF samples (100 µl) from healthy individuals (HC) and Alzheimer's disease (AD) patients were spiked with stable isotope‐labeled tau peptide standards containing the phospho‐epitopes pTau181, pTau231, pTau217, pTau205, and non‐phosphorylated Tau212‐221, and subjected to tryptic digestion. Desalted samples were fractionated by strong anion‐ and strong cation‐ exchange (SAX and SCX, respectively) solid phase extraction with step‐wise pH elution. The fractions were analyzed by parallel reaction monitoring on a nano‐flow LC‐MS on a Quadrupole‐Orbitrap hybrid mass spectrometer. Result: Several tau peptides were detected with both SAX and SCX, including pTau181, pTau217, pTau205, and Tau212‐221. The reproducibility of the new assay was assessed, and its performance was compared with PA‐based sample preparation and immunoassays for tau and pTau in a pilot study of AD patients and controls. Conclusion: The method described here allows for the detection of multiple tau/pTau peptides, while avoiding the need for selective protein isolation methods such as immunoaffinity enrichment or PA precipitation, thereby eliminating bias toward more/less soluble tau species. [ABSTRACT FROM AUTHOR]

Deregulation of the insulin‐like growth factor (IGF) axis and dysbalance of components of the IGF system as potential therapeutic targets have been described in different tumor types. IGF2 is a major embryonic growth factor and an important activator of IGF signaling. It is regulated by imprinting in a development‐ and tissue‐dependent manner and has been implicated in a broad range of malignancies including prostate cancer (PCa). Loss of imprinting (LOI) usually results in bi‐allelic gene expression and increased levels of IGF2. However, the regulatory mechanisms and the pathophysiological impact of altered IGF2 expression in PCa remain elusive. Here, we show that in contrast to many other tumors, IGF2 mRNA and protein levels were decreased in 80% of PCa in comparison with non‐neoplastic adjacent prostate and were independent of LOI status. Instead, IGF2 expression in both tumors and adjacent prostate depended on preferential usage of the IGF2 promoters P3 and P4. Decreased IGF2 expression in tumors was strongly related to hypermethylation of these two promoters. Methylation of the A region in promoter P4 correlated specifically with IGF2 expression in the 20% of PCa where IGF2 was higher in tumors than in adjacent prostate. We conclude that IGF2 is downregulated in most PCa and may be particularly relevant during early stages of tumor development or during chemotherapy and androgen deprivation. PCa differs from other tumors in that IGF2 expression is mainly regulated through methylation of promoter‐specific and not by imprinting. Targeting of promoter‐specific regions may have relevance for the adjuvant treatment of PCa. [ABSTRACT FROM AUTHOR]

Corn (Zea mays Glycine max predominantly produced in Iowa under rainfed conditions in which the amount and distribution of rainfall, and ambient air temperature, vary substantially among years. Prairie ecosystems also represent a small but significant portion of the landscape in the Midwest, but are subjected to the same variation in rainfall. Quantifying the effect of rainfall variation on ecosystem productivity is required to understand how the absence and the oversupply of water induces plant water stress and affects plant growth. We used the crop water stress index (CWSI) using canopy temperatures obtained from infrared temperature sensors coupled with eddy flux measurements to quantify the impact of water stress on corn, soybean, and prairie net ecosystem production (NEP) in central Iowa from June to August, 2006 through 2015. The relationships between CWSI and NEP, evapotranspiration (ET), and volumetric water content (VWC) were analyzed for these three canopies. Average seasonal CWSI values varied substantially among years and sites, indicating no-stress and extreme water stress periods. The CWSI significantly increased with decreasing ET and NEP, signaling that water stress adversely affected transpiration and C assimilation. Prairie CWSI was linearly and negatively related to VWC. Corn and soybean CWSI increased with very dry and wet soil moisture regimes, indicating that corn--soybean cropping systems were negatively affected by both the absence and oversupply of water. The CWSI approach quantifies water stress in different agroecosystems to compare the responsiveness of these systems to the dynamics of seasonal rainfall patterns. [ABSTRACT FROM AUTHOR]

Integrated population models ( IPMs) provide a unified framework for simultaneously analyzing data sets of different types to estimate vital rates, population size, and dynamics; assess contributions of demographic parameters to population changes; and assess population viability. Strengths of an IPM include the ability to estimate latent parameters and improve the precision of parameter estimates. We present a hierarchical IPM that combines two broad-scale avian monitoring data sets: count data from the North American Breeding Bird Survey ( BBS) and capture-recapture data from the Monitoring Avian Productivity and Survivorship ( MAPS) program. These data sets are characterized by large numbers of sample sites and observers, factors capable of inducing error in the sampling and observation processes. The IPM integrates the data sets by modeling the population abundance as a first-order autoregressive function of the previous year's population abundance and vital rates. BBS counts were modeled as a log-linear function of the annual index of population abundance, observation effects (observer identity and first survey year), and overdispersion. Vital rates modeled included adult apparent survival, estimated from a transient Cormack-Jolly-Seber model using MAPS data, and recruitment (surviving hatched birds from the previous season + dispersing adults) estimated as a latent parameter. An assessment of the IPM demonstrated it could recover true parameter values from 200 simulated data sets. The IPM was applied to data sets (1992-2008) of two bird species, Gray Catbird ( Dumetella carolinensis) and Wood Thrush ( Hylocichla mustelina) in the New England/Mid-Atlantic coastal Bird Conservation Region of the United States. The Gray Catbird population was relatively stable (trend +0.4% per yr), while the Wood Thrush population nearly halved (trend −4.5% per yr) over the 17-yr study period. IPM estimates of population growth rates, adult survival, and detection and residency probabilities were similar and as precise as estimates from the stand-alone BBS and CJS models. A benefit of using the IPM was its ability to estimate the latent recruitment parameter. Annual growth rates for both species correlated more with recruitment than survival, and the relationship for Wood Thrush was stronger than for Gray Catbird. The IPM's unified modeling framework facilitates integration of these important data sets. [ABSTRACT FROM AUTHOR]

Engineered soil mixes are expected to maintain plant growth while minimizing nutrient leaching in greenhouse and bioretention applications. Iron (Fe) has been suggested within plant growth mixtures as a sorbent for phosphorus. The purpose of this study was to determine if Fe filings are an appropriate component of engineered plant growth mixtures. Iron filings were added to engineered soil mixes in laboratory columns, and plants were grown for 2 mo. Unfortunately, Fe filings partially cemented the engineered mixes, especially the treatment with sand and compost but no soil. After completing the study, orange and red aggregates were apparent. Although Fe filings might be useful in filter beds, they were not suitable within engineered plant growth mixes. [ABSTRACT FROM AUTHOR]

Models of instantaneous soil-surface CO2 efflux (SCEins) are critical for understanding the potential drivers of soil C loss. Several simple SCEins models have been reported in the literature. Our objective was to compare and validate selected soil temperature (Ts)-and water content (θv)-based equations for modeling SCEins among a variety of cropping systems and land management practices. Soil-surface CO2 effluxes were measured and modeled for grain-harvested corn (Zea mays L.)-soybean [Glycine max (L.) Merr.] rotations, grain- and stover-harvested continuous corn systems with and without a cover crop, and reconstructed prairies with and without N fertilization on soils with subsurface drainage. Soil-surface CO2 effluxes, Ts, and θv were measured from 2008 to 2011. Models calibrated with weekly measured SCEins, Ts, and θv throughout the growing season produced lower root mean squared error (RMSE) than models calibrated with several weeks of hourly measured data. Model selection significantly affected SCEins estimations, with models that use only Ts parameters having lower RMSE than models that use both Ts and θv. However, the model that produced the lowest RMSE during validation estimated growing-season SCE that did not significantly differ from numerical integration of weekly measured SCEins. All models had similar residual errors with autocorrelated trends at monthly, weekly, and hourly scales. Autoregressive moving average functions were able to precisely describe the temporal errors. To accurately model SCEins and scale across time, improvement of temporal errors in Ts- and θv-based SCEins models is needed to obtain accurate and precise closure of C balances for managed and natural ecosystems. [ABSTRACT FROM AUTHOR]

Objective To compare the impact of common surgical interventions (selective dorsal rhizotomy, muscle-tendon surgery, and osteotomies) for patients with cerebral palsy (CP) on Gross Motor Function Measure and temporal, kinematic, and kinetic gait variables as assessed via 3-dimensional motion analysis. Design Retrospective cohort study. Setting Motion analyses laboratory. Participants Ninety-four patients with CP, 56 of whom underwent surgery (37, muscle-tendon surgery; 11, osteotomy; and 8, selective dorsal rhizotomy) and 38 of whom did not have surgery; the patients were ages 4-18 years, with a Gross Motor Function Classification System classification of I, II, or III. Interventions Single-event, multilevel muscle tendon surgery, selective dorsal rhizotomy, and osteotomy. Main Outcome Measures Change scores (postintervention – preintervention) in Gross Motor Function Measure and temporal, kinematic, and kinetic gait variables. Results No statistically significant differences in change scores were found between groups in the Gross Motor Function Measure, velocity, or stride length measures after the observation period. The selective dorsal rhizotomy group had greater improvements in knee extension when compared with the nonsurgical group and greater hip and knee total range of motion during the gait cycle when compared with nonsurgical group and the muscle-tendon surgery and osteotomy cohorts. Lastly, the muscle-tendon surgery group had greater improvements in total knee range of motion compared with the nonsurgical group. Conclusions Patients who undergo selective dorsal rhizotomy and, to a lesser extent, muscle tendon procedures demonstrate greater improvements in kinematic gait variables compared with nonsurgical interventions in patients with spasticity resulting from CP. [ABSTRACT FROM AUTHOR]

Background Alkaline phosphatase ( ALP) is an important serum marker in primary sclerosing cholangitis ( PSC). Patients with obstruction of the large bile ducts due to dominant strictures ( DS) are a special, clinically important phenotype. Aim To determine the impact of ALP reduction on liver transplantation-free survival in PSC patients with DS. Methods Prospective cohort study in 215 PSC patients. We performed subgroup analysis for patients without DS (no DS, n = 84), DS at first presentation ( DS early, n = 72) and development of DS during the course of the study ( DS late, n = 59). We evaluated two scores of ALP reduction. ALP reduction 1 was defined as ALP normalisation, 50% reduction compared with baseline values, or reduction below 1.5 times of upper limit of normal ( ULN) within 6 months. ALP reduction 2 was defined as ALP reduction below 1.5 times of ULN within 12 months. Results Of the patients, 59.5% reached an ALP reduction 1 and 56.7% according to ALP reduction 2. Achievement of each score was associated with longer transplantation-free survival in all three groups ( ALP reduction 1: no DS P = 0.001; DS early P < 0.001; DS late P = 0.022; ALP reduction 2: no DS P = 0.014; DS early P = 0.001; DS late P = 0.002). Cox-regression analysis revealed each score as an independent predictor for improved transplantation-free survival ( ALP reduction 1 and 2 P < 0.001 each). We further analysed previously published scores of ALP improvement in PSC showing also improved survival in patients with ALP normalisation or a reduction below 1.5 times of ULN ( P = 0.003, P = 0.001, respectively), whereas the score determined by 40% reduction did not show significant differences in survival ( P = 0.55). Conclusions Reduction in alkaline phosphatase values within the first year is associated with improved transplantation-free survival in patients with primary sclerosing cholangitis independent of the presence of dominant strictures. Alkaline phosphatase might be an adequate surrogate marker for outcome assessment in clinical studies both for patients with and without dominant strictures. [ABSTRACT FROM AUTHOR]

Grain sorghum [Sorghum bicolor (L.) Moench] is an important dryland crop in southeastern Colorado, but expansion into northeastern Colorado is thought to be limited due to the shorter growing season. The study examined whether sorghum production could be expanded into northeastern Colorado. A 2-yr study in northeastern Colorado at Akron (2010, 2011), Fort Collins (2011), and Stratton (2010) investigated row orientation, seeding rate, and row spacing effects for three hybrids within early to medium-early maturity classes on the time to physiological maturity and grain yield. All treatments reached physiological maturity in the four trial environments. Hybrid selection and seeding rate significantly impacted the thermal time to reach physiological maturity. The medium-early hybrid (5745) matured significantly later than the early maturity hybrids (88P68 and DKS29-28). The seeding rate of 20 seeds m-2 matured significantly earlier than 11 seeds m-2, which matured much earlier than 3 seeds m-2. Row orientation and row spacing did not influence maturity. Yields were generally acceptable across all environments, hybrids, and agronomic treatments, and average yields among environments ranged from 1690 to 4845 kg ha-1. Probabilities of the hybrids reaching maturity were high at Akron and Stratton (at least 62 and 86%, respectively, for the latest simulated planting date), but low for Fort Collins (highest of 75% for the earliest simulated planting date). Grain sorghum can successfully be grown in northeast Colorado, especially if planting early maturity hybrids using 0.76 m row spacing at a seeding rate close to 11 seeds m-2. [ABSTRACT FROM AUTHOR]

Vineyards in the southeastern United States face challenges including poor internal soil drainage, high precipitation, and warm temperatures. This environment causes elevated humidity, creating ideal conditions for fungal diseases. Maintaining tall fescue (Schedonorus arundinaceus Shreb) and resident vegetation ground cover in vineyard inter-rows is a common cultural practice in the region, believed to benefit grape (Vitis vinifera L.) production by increasing competition for soil water and thereby favorably reducing vine vegetative growth. We hypothesized that, although inter-row fescue may reduce soil water availability, it may also increase humidity within the vineyard. Our objectives were to assess surface vapor flux from two inter-row treatments (bare soil and tall fescue) and to determine any corresponding effects on soil water content and humidity within the inter-row. Surface vapor flux, soil water content, and vapor pressure (30 cm height aboveground) were measured in inter-rows subjected to each treatment. Observed surface vapor flux for fescue inter-row exceeded that of bare soil by a daily average of 1.1 mm during the grape growing season. Despite fescue inter-row evapotranspiration (ET), soil water depletion was insufficient to produce stress in the vines. Fescue inter-row vapor pressure increased compared to bare soil inter-rows by an average of 2% (P< 0.09) during the growing season. Data suggest that fescue ET may increase inter-row humidity in warm, humid environments, while providing only modest influence on soil water availability. Additional work including increased plot size to accommodate fetch for microclimate measurements, and biological assessment of humidity implications for disease is warranted. [ABSTRACT FROM AUTHOR]

Background A recent genome-wide association study identified the FUT2 secretor status and genotype defined by the single-nucleotide polymorphism rs601338 as potential genetic risk factor in primary sclerosing cholangitis ( PSC), which significantly influences biliary bacterial composition. Aim To determine the impact of the rs601338- FUT2 genotype on frequency of biliary infections, development of dominant stenosis and liver-transplantation-free survival in patients with PSC. Methods Cohort study of 215 patients with PSC treated at our tertiary care centre with respect to their rs601338- FUT2 genotype. Results of endoscopic retrograde cholangiography and bile culture were analysed; 639 biliary samples were obtained, cultured and subjected to microbial analysis. Clinical and laboratory data were analysed using chart reviews. Results For the rs601338- FUT2 genotype, 69 patients (32.1%) were found to be wildtype ( GG), 97 (45.1%) patients were heterozygous ( AG) and 49 patients (22.8%) were homozygous-mutated ( AA). In addition to alterations in the bacterial pattern, especially in heterozygous carriers, patients with mutated alleles had a marked increase in the frequency of biliary Candida infections ( P = 0.025). Further, patients with mutated alleles showed an increased frequency of episodes of cholangitis ( P = 0.0025), development of dominant stenosis ( P < 0.002) and a reduced actuarial transplantation-free survival ( P = 0.044). Levels of biliary Ca19-9 were significantly elevated in the homozygous-mutated patients. Conclusions The rs601338- FUT2 genotype is strongly associated with episodes of cholangitis, fungobilia and the incidence of dominant stenosis, which are three clinical hallmarks of PSC; FUT2 is thus an important genetic risk factor for host-microbial diversity and disease progression in PSC. [ABSTRACT FROM AUTHOR]

Abstract: Vibrio cholerae, the causative agent of cholera, releases several virulence factors including secreted proteases when it infects its host. These factors attack host cell proteins and break down tissue barriers and cellular matrix components such as collagen, laminin, fibronectin, keratin, elastin, and they induce necrotic tissue damage. The secreted protease PrtV constitutes one virulence factors of V. cholerae. It is a metalloprotease belonging to the M6 peptidase family. The protein is expressed as an inactive, multidomain, 102 kDa pre-pro-protein that undergoes several N- and C-terminal modifications after which it is secreted as an intermediate variant of 81 kDa. After secretion from the bacteria, additional proteolytic steps occur to produce the 55 kDa active M6 metalloprotease. The domain arrangement of PrtV is likely to play an important role in these maturation steps, which are known to be regulated by calcium. However, the molecular mechanism by which calcium controls proteolysis is unknown. In this study, we report the atomic resolution crystal structure of the PKD1 domain from V. cholera PrtV (residues 755–838) determined at 1.1 Å. The structure reveals a previously uncharacterized Ca2+-binding site located near linker regions between domains. Conformational changes in the Ca2+-free and Ca2+-bound forms suggest that Ca2+-binding at the PKD1 domain controls domain linker flexibility, and plays an important structural role, providing stability to the PrtV protein. [Copyright &y& Elsevier]

Cytomegalovirus ( CMV) can cause severe infections with serious consequences in renal transplant recipients. Disseminated CMV infections can affect almost every organ, but obstructive cholestasis and cholangitis, as a consequence of a CMV-induced papillitis, is extremely rare. We are reporting a rare case of obstructive cholestasis and cholecystitis due to CMV-related inflammation of the major duodenal papilla in a 60-year-old woman 3 months after renal transplantation. In addition, the patient suffered from a disseminated CMV infection with ulcerative esophagitis and gastritis. Because of the severe CMV infection, failure of the renal graft occurred. Obstructive cholestasis was resolved through internal stenting, and the progressive cholecystitis necessitated an emergency cholecystectomy. Following antiviral therapy with ganciclovir, the gastrointestinal ulcerations regressed and renal function was restored. Diagnosis of the CMV-related disease was established only in tissue samples, whereas standard serologic tests had failed. [ABSTRACT FROM AUTHOR]

Terrestrial mud volcanoes ( TMVs) represent geochemically diverse habitats with varying sulfur sources and yet sulfur cycling in these environments remains largely unexplored. Here we characterized the sulfur-metabolizing microorganisms and activity in four TMVs in Azerbaijan. A combination of geochemical analyses, biological rate measurements and molecular diversity surveys (targeting metabolic genes aprA and dsrA and SSU ribosomal RNA) supported the presence of active sulfur-oxidizing and sulfate-reducing guilds in all four TMVs across a range of physiochemical conditions, with diversity of these guilds being unique to each TMV. The TMVs varied in potential sulfate reduction rates ( SRR) by up to four orders of magnitude with highest SRR observed in sediments where in situ sulfate concentrations were highest. Maximum temperatures at which SRR were measured was 60° C in two TMVs. Corresponding with these trends in SRR, members of the potentially thermophilic, spore-forming, Desulfotomaculum were detected in these TMVs by targeted 16 S rRNA analysis. Additional sulfate-reducing bacterial lineages included members of the Desulfobacteraceae and Desulfobulbaceae detected by aprA and dsrA analyses and likely contributing to the mesophilic SRR measured. Phylotypes affiliated with sulfide-oxidizing Gamma- and Betaproteobacteria were abundant in aprA libraries from low sulfate TMVs, while the highest sulfate TMV harboured 16 S rRNA phylotypes associated with sulfur-oxidizing Epsilonproteobacteria. Altogether, the biogeochemical and microbiological data indicate these unique terrestrial habitats support diverse active sulfur-cycling microorganisms reflecting the in situ geochemical environment. [ABSTRACT FROM AUTHOR]

Abstract: Time to freezing tumor tissue for RNA expression analysis will always vary to some extent. To evaluate the effect of ischemia time, tumor tissue from ten breast cancer patients was collected and aliquots of tissue were snap frozen at different time points after surgery (0, 0.5, 1, 3 and 6 h). Using miRNA and mRNA expression microarrays and statistical analysis, 56 miRNAs and 1788 mRNAs were found to be significantly altered with ischemia time up to six hours. Several of the 56 miRNAs have been reported to play a role in cancer, such as hsa-miR-663 and hsa-miR-125a-3p. Known stress response genes such as GADD45B, JUND and FOSB were among the mRNAs most significantly affected by time to freezing. A novel statistical method for identification of consistently correlated miRNA–mRNA pairs and miRNA-associated biological processes in time course data is presented. Application of this method revealed that several miRNAs, including hsa-miR-1228, hsa-miR-1225-5p and hsa-miR-574-5p, were associated through their correlation to mRNAs to biological processes such as “response to stimulus” and “stress response”. These miRNAs also showed enrichment of predicted targets among either their positively or negatively correlated mRNAs. The induced miRNAs may play both direct and indirect roles in biological responses. Caution should be taken when the miRNAs and mRNAs reported to be affected by ischemia time are included in a prognostic or predictive signature. [Copyright &y& Elsevier]

Introduction: A heavier weight in adults is becoming the norm rather than an abnormal weight. Whether the same trend is happening in children is unknown. Objective: To assess the perception of the weight of 4- to 5-year-old children and the recognition of overweight by both parents. Design: Population-based survey. Participants: A questionnaire was sent to parents of 1155 4- to 5-year-old children. Results: In total, 439 questionnaires (35%) were returned. Of all, 90% of the children had a normal weight, 9.3% were overweight and 4.1% were obese. For all weight classes, the parents depicted the child as lighter on both the verbal and visual scale. Of all, 75% of mothers of overweight children stated that the child had a normal weight. In obese children, 50% of the mothers believed that the child had a normal weight. Conclusion: Children with a weight in the normal range were considered by their parents as a little too light or too light. Overweight was considered as normal weight, and obesity as normal or a little too heavy. The perception of a normal weight in children at 4–5 years is distorted. [ABSTRACT FROM AUTHOR]

Acute liver failure is a life threatening disease mostly triggered by drug-induced or toxic liver damage or viral hepatitis. Herpes Simplex virus (HSV) hepatitis is rare and accounts for only 1% of all acute liver failures. The importance of HSV-induced acute liver failure is based on its extremely severe clinical course with lethality rates of almost 75%. HSV hepatitis is just one of several clinical manifestations of HSV sepsis leading more frequently to encephalitis, pneumonia and esophagitis. Local herpes infection or recurrence of dermal lesions (herpes labialis, herpes genitalis), however, is common and account for the high prevalence of HSV-1 or HSV-2 infection in adults. Another rare entity is visual dissemination, which mostly affects immunocompromised patients. Compromised cellular immunity is a major risk factor for HSV sepsis because of either primary infection or reactivation of occult chronic HSV infection. Delayed diagnosis without antiviral therapy significantly contributes to the unfavorable outcome. Typically, anicteric hepatitis is seen in patients with HSV hepatitis. Because of its low incidence, however, and the lack of dermal manifestations, HSV hepatitis is rarely considered in the context of acute liver failure. In addition, diagnostic tests might not always be available. Therefore, it is a generally accepted consensus to begin antiviral therapy pre-emptively with acyclovir in cases of acute liver failure of unknown origin, in which high urgency (HU) liver transplantation remains the only therapeutical option. Even in the case of early specific therapy, sepsis may prevail and the indication for HU transplantation must be evaluated carefully. The outcome after liver transplantation for HSV-induced liver failure with reported survival rates of more than 40% is good. Because of the risk of recurrence, lifelong prophylaxis with acyclovir is recommended. [ABSTRACT FROM AUTHOR]

The aim of this study is to report our interventional radiologic procedures (IRP) in liver transplant (LTX) patients. These include procedures for biliary, arterial, venous, and portal complications, as well as the treatment of infected and non-infected fluid collections. This retrospective study covered 583 patients (mean age: 44 ± 14 yr) in whom a total of 685 LTX were performed from August 1987 to April 2005. Overall, 182 LTX patients underwent a total of 428 IRP, including digital subtraction angiography (n = 152/35.51%), percutaneous transluminal angioplasty (PTA) (n = 4/0.93%) and PTA + stent (n = 7/1.63%) of arterial anastomosis, PTA + stent of the celiac trunk (n = 2/0.46%), transjugular intrahepatic portosystemic shunt (TIPS) (n = 2/0.46%), arterial lysis (n = 4/0.93%), venous lysis (n = 2/0.46%), inferior vena cava stenting (n = 2/0.46%), percutaneous biliary drainage (n = 34/7.94%), percutaneous transluminal dilatation (PTD) of the choledocho-enteric anastomosis (n = 16/3.73%), biliary stent (n = 5/1.16%), intrahepatic biliary flushing treatment, stone and cast biliary extraction (n = 27/6.30%), other interventions (e.g., embolization in other regions, transjugular liver biopsies, lymphangiographies) (n = 9/2.10%), and ultrasound- and computer tomography-guided biopsies and percutaneous drainage (n = 153/35.74%). The overall success rate was 85.7%. Technical improvements in LTX and interventional radiology permit vascular and biliary complications to be treated successfully by interventional radiology. [ABSTRACT FROM AUTHOR]

Although heart failure (HF) is equally prevalent in men and women, women with HF are more likely to report decreased quality of life and are more likely to die of the disease compared with men. Moreover, HF has been studied less extensively in women and no study has specifically addressed women with New York Heart Association (NYHA) class III HF using a qualitative method. This pilot study sought to gain insight into the lived experience of women with NYHA class III HF. Using a phenomenological approach, interviews obtained from 4 middle-aged women with NYHA class III HF were analyzed using the Giorgi method of data analysis. Five themes emerged: (1) developing a new conception of self, (2) conceding physical limitations, (3) enduring emotional heartache, (4) accepting support, and (5) rejuvenating through rest. This study provides a beginning to our understanding of the lived experience of women with NYHA class III HF. However, further exploration is needed to increase our knowledge of HF in women, particularly among diverse populations. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the use of prescribed fire as a management tool to reduce fuel loads on public lands in forested areas in the western U.S. The study found that identifying the impacts of prescribed fire on bird communities in ponderosa pine forests is necessary for providing land management agencies. According to the study, the usefulness of a Bayesian hierarchical model for identifying effects of habitat disturbances on wildlife communities is described. It states that the methods can be used to provide guidance for future management activities by land management agencies.

Background: A substantial proportion of the decisions to withhold or withdraw life-prolonging treatment are based on the newborn's predicted poor quality of life. All previous studies on end-of-life decisions were done in countries with adequate support for disabled neonatal intensive care units (NICU) survivors. Data on quality-of-life considerations in countries with developing health care are not available yet. Aim: The aim of the study was to examine the considerations of physicians taking end-of-life decisions in sick newborns and how those decisions are carried out in practice in a less developed health care setting. Method: Thirty-two deaths over 18 months in a neonatal unit were retrospectively analyzed. Results: Twenty-four deaths (75%) were attributable to withholding or withdrawing of treatment. In 7 of these cases (29%), the decisions were based on quality-of-life considerations, mostly predicted suffering and expected hospital dependency. For the majority of paediatricians, end-of-life decision making was not influenced by legal or economic considerations or by considerations regarding availability of supportive care after discharge. Conclusion: Our study suggests that physician end-of-life decision making in this unit in a less developed health care setting is found to be similar to that in developed health care settings and is independent of availability of supportive care after discharge for infants with disabilities. [ABSTRACT FROM AUTHOR]

Enormous advancements in visceral transplantation have led to significant improvements in the quality of life of patients. However, despite these developments, the average graft half-life after transplantation has remained almost unchanged and chronic rejection is still considered a major problem. In this regard, more concerns have shifted to factors influencing long-term graft survival, patient survival, and quality of life. To achieve this goal, detrimental effects of immunosuppressive (IS) agents, which have deleterious influence on the quality of life and/or patient survival, should be reduced. In the course of recent years, the transplant community has worked on reducing these side effects by developing new ISs, employing new combination regimens, or finding and adjusting optimal dosages and blood level concentrations. Among the IS agents, the antifungal, antitumoral and IS activity of mammalian target of rapamycin (mTOR) inhibitors without nephrotoxicity, have received special attention regarding this new class of IS. Sirolimus (SRL), as the first member of mTOR inhibitors, has been utilized in many clinical trials with respect to its benefit-risk assessment. In our review, the clinical evolution of SRL, as well as the evidence-based clinical benefits of SRL in kidney and liver transplantation (KTx, LTx), are summarized. Various studies of SRL in KTx and LTx have shown that combination therapy with SRL will enrich the variety of IS modalities. It also can be regarded as a safe base therapy to which other necessary drugs can be added. In addition to the enhanced acute rejection prophylaxis, and in contrast to the calcineurin inhibitors (CNI) and steroids, this drug solely does not have common side effects such as nephrotoxicity, neurotoxicity, diabetes mellitus and hypertension. Moreover, this agent might diminish vasculopathic processes that mediate chronic allograft nephropathy (CAN). Therefore, by reducing the likelihood of CAN it can decrease the rate of long-term organ failure. One possibly desirable characteristic of SRL is its antiproliferative effect, which could provoke antitumoral or antiatherogenic activity following transplantation. Despite all promising impacts of SRL in organ transplantation, there are some concerns regarding the adverse effects of this drug, for instance dyslipidemia, pneumonitis and wound healing problems. However, the majority of these side effects can be reduced or ceased by careful dose adjustments and correct timing of use. In conclusion, after a decade of both in vivo and in vitro studies on SRL, it can be advocated that SRL is a promising, potent and effective IS agent as it reduces the rate of acute rejection episodes in de novo transplants. It could improve the quality of life, graft and patient survival rate, and achieve excellent outcomes with few adverse effects when wisely used in combination with other immunosuppressants. [ABSTRACT FROM AUTHOR]

Biliary complications remain a substantial cause of morbidity following liver transplantation. They have been reported to occur in a rate of 10–15% of full-size transplantations and may be higher in living donor, split or reduced size liver transplantations. The most common biliary complications following liver transplantations are leaks and strictures. In both, the incidence varies with respect to type of graft and donor as well as the type of biliary anastomosis. The management of the biliary complications requires a multidisciplinary approach and has changed over the past decade, favoring endoscopic and radiological techniques. Surgical revision including retransplantation is reserved for patients in whom endoscopic and interventional modalities are unsuccessful. [ABSTRACT FROM AUTHOR]

In a previous study, Dutch children with phenylketonuria (PKU) were found to be slightly shorter than their healthy counterparts. In the literature, it has been hypothesized that a higher protein intake is necessary to optimize growth in PKU patients. The study aimed to investigate whether protein intake (total, natural and protein substitute) in this group might be an explanatory factor for the observed growth. Growth of height and head circumference and dietary data on protein intake (total, natural and protein substitute) from 174 Dutch PKU patients born between 1974 and 1996 were analysed retrospectively for the patients' first 3 years of life. Analyses were corrected for energy intake during the first year of life and for the clinical severity of the deficiency of phenylalanine hydroxylase by means of plasma phenylalanine concentration at birth. Neither protein nor energy intake correlated with height growth. A positive, statistically significant relation between head circumference growth and natural protein and total protein intake was found, but not with the intake of the protein substitute or energy. Therefore, this study suggests that improvement of the protein substitute rather than an increase of total protein intake may be important in optimizing head circumference growth in PKU patients. [ABSTRACT FROM AUTHOR]

This article focuses on a study of air bubbling and dietary sulfur reduction to mitigate hydrogen sulfide and odor from swine waste. Modern swine operations generate large volumes of slurry. The slurry is usually stored in earthen or concrete structures in an anaerobic condition that can produce toxic gases particularly during agitation and removal. When the slurry is disturbed during the agitation process, reduced sulfurs, volatile organic compounds, phenols, and others are suddenly released through off-gasing. The primary objective of this study was to evaluate, at the bench scale, the two potential methods for reducing hydrogen sulfide emissions from swine manure slurry. Bench-scale methods offer much greater control over experimental and environmental variables than do production-scale studies, in which potential treatment effects of diet on manure emissions are often masked or confounded. The objective was addressed through two experiments: in the first, air was bubbled at low rates through stored manure slurry and hydrogen sulfide emission rates were measured during a 4-week period; in the second, dietary sulfide was adjusted and hydrogen sulfide and odor emission rates were measured from the stored slurry.

The article presents a Bayesian approach to the problem of surveys collecting count data while providing an example of its implementation a spatial model of predicted abundance for the Cerulean warbler. The use of autoregressive term representing potential correlation between adjacent route counts is tackled. The provision of a basis for the development of management programs for the functional relationships elucidated for the Cerulean warbler is outlined.

Evidence from previous studies has suggested that the inter-individual differences in human brain-wave patterns (EEG) are predominantly determined by genetic factors. In particular, the within-pair EEG concordance of monozygotic (mz) twins was found to be typically as high as r = 0.81 across channels and frequency bands, thus being comparable to that between repeated assessments on the same individual with typically r = 0.83. Yet our investigations into mz twins discordant and concordant for schizophrenia yielded a significantly reduced within-pair EEG concordance for both, the pairs discordant for schizophrenia and the pairs concordant for schizophrenia (with concordance for schizophrenia assessed through a syndrome-oriented approach). A multivariate discriminant function of EEG parameters distinguished in a reproducible way between affected and unaffected subjects at an overall performance of >75% correctly classified subjects, while the severity of illness, as derived from EEG-differences between affected and unaffected subjects, was closely related to the severity of illness as provided by psychopathology syndrome scores. Consequently, EEG anomalies associated with schizophrenia and manifested differently in the mz co-twins concordant for schizophrenia are likely the effect of nongenetic, pathologic processes that evolved independently in the co-twins' genetically identical brains once the illness began to progress. The existence of such nongenetic processes would suggest a modification of the standard phenotype-to-genotype search strategies of molecular-genetic studies that aim to link the schizophrenia phenotype to genetic vulnerability factors. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

To document changes in antibiotic resistance of organisms in cases of equine bacterial ulcerative keratitis over a 10-year time period. A retrospective study. Medical records of equine patients with bacterial ulcerative keratitis seen at the University of Florida's VMTH for the years 1991–2000 were reviewed. All cases of equine bacterial ulcerative keratitis for the above mentioned years were examined. Bacterial isolates were identified and subjected to Kirby-Bauer disc diffusion method sensitivity tests. Antibiotics used in the sensitivity tests included bacitracin, ampicillin, gentamicin, chloramphenicol, polymyxin B, trimethoprim-sulfa, neomycin, kanamycin, carbenicillin, tobramycin and enrofloxacin. A total of 65 bacterial isolates were subjected to sensitivity testing. Of these isolates, Pseudomonas aeruginosa accounted for 14 of the bacterial isolates (22%), Streptococcus equi subspecies zooepidemicus accounted for 13 of the bacterial isolates (20%), and Staphylococcus aureus accounted for four of the isolates (6%). A statistically significant increase in resistance of Pseudomonas aeruginosa isolates to the antibiotics gentamicin and tobramycin was found between the isolates from 1992 to 1998 and those from 1999 to 2000. An increase in resistance of Streptococcus equi subspecies zooepidemicus to gentamicin was found between the isolates from 1993 to 1997 and those from 1998 to 2000. Streptococcus equi subspecies zooepidemicus and Pseudomonas aeruginosa were the most common organisms isolated from cases of equine bacterial keratitis referred to the University of Florida's VMTH for the years 1991–2000. There appears to be an increase in resistance of Streptococcus equi subspecies zooepidemicus to gentamicin over the past 10 years. In addition, there is a significant increase in resistance of Pseudomonas aeruginosa to both gentamicin and tobramycin over the same time period. [ABSTRACT FROM AUTHOR]

Abstract Background Ursodeoxycholic acid (UDCA) and its taurine conjugate (TUDCA) exert a protective effect in cholestatic liver diseases. A greater hepatoprotective effect of TUDCA has been suggested. Absorption appears to be a limiting factor and up to now has not been studied in man. Methods We studied absorption and biliary bile acid secretion and composition after administration of UDCA and TUDCA in patients who had complete extrahepatic biliary obstruction caused by pancreatic carcinoma but had no intestinal or liver disease. After 5 days of intact enterohepatic circulation eight patients with a percutaneous biliary–duodenal drainage received, during two study periods, 1000 mg (1916·9 µmol; mean 29·6 µmol kg-1 ) TUDCA and 750 mg (1910·4 µmol; mean 29·5 µmol kg-1 ) UDCA in random order. Each patient served as his own control. Results After UDCA and TUDCA administration the biliary UDCA content increased to 55·2% and 54·6% of total bile acids, respectively (not significant). Biliary secretion of cholic and chenodeoxycholic acids remained unchanged whereas that of lithocholic acid increased slightly. A total of 64·6% of the orally administered TUDCA and 55·1% of the UDCA was absorbed (not significant). After TUDCA administration, biliary UDCA was preferentially (95·4%) taurine-conjugated whereas after UDCA administration biliary UDCA was mainly (79·8%) glycine-conjugated. Conclusions After oral administration of TUDCA and UDCA, no significant differences in their absorption and in biliary bile acid secretion exist. Whether biliary enrichment with taurine conjugates of UDCA instead of glycine conjugates offers advantages in the treatment of cholestatic liver disease is unclear at present. [ABSTRACT FROM AUTHOR]

Glycogen storage disease type I (GSD I) (McKusick 232200) is caused by inherited defects of the glucose-6-phosphatase complex. Patients with GSD Ia as well as patients with GSD Ib may suffer from intermittent diarrhoea, which seems to worsen with age. The cause of this diarrhoea is unknown. This study describes the results of investigations of intestinal functions and morphology in patients with GSD Ia and GSD Ib, which were performed to detect a common cause for chronic diarrhoea in GSD I. The following were investigated: faecal fat excretion, faecal α1-antitrypsin and faecal chymotrypsin, expiratory H2 concentrations, persorption of cornstarch in urine and colonic biopsies. With the investigations presented in this study, no common cause for diarrhoea in GSD I was found. In GSD Ib loss of mucosal barrier function due to inflammation, documented by increased faecal α1-antitrypsin excretion (3.5–9.6 mg/g dry faeces) and inflammation in the colonic biopsies, seems to be the main cause. The inflammation is most likely related to disturbed neutrophil function, which is often found in GSD Ib. Whether another cause is involved in GSD Ia and in GSD Ib, related to the disturbed function of glucose-6-phosphatase in the enterocyte, remains to be investigated. [ABSTRACT FROM AUTHOR]

This article reports a study that was carried out in 6 German advanced mechanical engineering organizations. The research investigated the wider role of the CNC machine operator against the background of an increased focus on quality management issues and lean production. Fifty-one interviews were carried out with individuals from different professional groups. The results showed that operators had an important function in compensating for variations in the manufacturing process. The choice of operator actions was influenced by several production-related factors (e.g., tolerance limit). Furthermore, we identified several organizational boundaries that indicated a considerable potential for efficiency gains if collaboration across these boundaries could be improved. © 2000 John Wiley & Sons, Inc. [ABSTRACT FROM AUTHOR]

The article discusses how relative species richness can have a positive impact on local businesses and urbanization, and mentions the capture-recapture models which can be used to estimate specie richness. It discusses the impact of urbanization on relative richness of avian communities in the U.S. and states that capture-recapture models are also useful for ecosystem management and nature conservation.

In the Ozark Highlands of the USA (36–38° N, 91–95° W), annual application of poultry litter to pasture land is a routine waste management practice. The objective of this study was to measure the effect of site characteristics and poultry litter application on runoff and nutrient transport from grazed pasture and forest sites at different landscape positions. Sixteen pairs of 1 × 2 m plots were established on Nixa (loamy‐skeletal, siliceous, active, mesic Glossic Fragiudults) and Clarksville (loamy‐skeletal, siliceous, semiactive, mesic Typic Paleudults) cherty silt loams. One plot of each pair received 4.5 Mg ha−1 of poultry litter. Rainfall was simulated at 75 mm h−1 for 1 h (25‐yr return period storm) one month after litter application. A composite runoff sample was analyzed for dissolved reactive phosphorus (DRP), total phosphorus (TP), ammonia N (NH3‐N), nitrate N (NO3‐N), total Kjeldahl nitrogen (TKN), and total suspended solids (TSS). Poultry litter‐treated plots had consistently higher concentrations of all water quality parameters tested compared to untreated plots. Concentration of DRP in runoff from untreated plots was linearly correlated with three soil P tests (0.35 < r2 < 0.85). Soil P on litter‐treated plots had little effect on runoff DRP, which averaged 2.20 mg L−1. High variation in runoff resulted in only NO3‐N showing significantly greater losses due to poultry litter treatment at two pasture sites. Results indicate that variation in runoff has a significant effect on nutrient transport from grazed pastures receiving poultry litter. [ABSTRACT FROM AUTHOR]

Background: There is mounting evidence that lifestyle interventions and behavioural changes play a significant role in maintaining cognition and function, as well as preventing dementia. Consequently, it is important that clinicians confronted with subjects with early cognitive concerns, have appropriate tools available to assist in diagnosis and to facilitate risks management appropriately. The application of polygenic risk score (PRS) tests has the potential to contribute towards management planning and to reduce the burden of testing in subjects with low overall risk. Methods: This retrospective analysis considered the application of genoSCORETM in a small cohort of patients seen over a six month period in a London Memory Clinic. The test was offered to selected patients in the clinic with MCI not clinically attributable to dementia, or cognitively normal individuals concerned about their risks of dementia. The impact upon clinical management and lifestyle modification was reviewed. genoSCORE, a polygenic risk score algorithm, was developed by Cytox to assess genetic risk for the future development of Late‐Onset Alzheimer's disease (LOAD). Results: Patients receiving the genoSCORE test included those with early MCI, subjective memory complaints and a small number concerned about their risk of dementia. In each case, a medical history was taken and individuals assessed using the Addenbrooke's Cognitive Examination, conducted either in clinic or remotely. genoSCORE polygenic risk score was easy to conduct and well received. The results stimulated individuals at risk of developing LOAD to make lifestyle adjustments and thereby potentially modifying their dementia risk. Conclusions: In this study, the genoSCORE PRS test provided a valuable assessment of genetic risk of individuals most likely to decline cognitively decline towards AD and as such, contributed significantly to clinical management decisions. The ease and effectiveness of home sampling of saliva as source DNA for the PRS test was a major factor and well aligned with the continuing need for remote consultations in the light of COVID‐19 concerns. Further larger‐scale studies to determine the full clinical and associated economic impact of the genoSCORE PRS test are required. [ABSTRACT FROM AUTHOR]

The article focuses on a study conducted to examine animal species richness, extinction and colonization. To estimate species richness from species count and presence-absence data, probabilistic capture-recapture models have been used recently. The vital rates responsible for changes in animal communities over time were analyzed using estimators.

Examines the application of the North American Breeding Bird Survey (BBS) to estimate the population change from count data. Description of the BBS; Details on issues related to the analysis of count data; Information on analytic methods used for BBS and other count data; Illustration of the process of model selection using data from the Carolina Wren.